Exposure to Wastewater Effluent Reshapes Brain-Gonad-Sperm Neurochemistry and Impairs Sperm Function in a Wild Fish Population

Pharmaceuticals are ubiquitous in treated wastewater, yet their chronic effects on fish neurochemistry and reproduction in the wild remain poorly understood. Here, we combined targeted LC-HRMS with brain-gonad-sperm neurotransmitter (NT) profiling, bioaccumulation analysis, histopathology, and sperm quality assessment in European perch (Perca fluviatilis) inhabiting an effluent-fed pond and a reference pond over 2 years. Forty-one pharmaceuticals were detected in water, with significantly higher richness and concentrations in the effluent-fed pond. Fish from this pond exhibited progressive, tissue-specific bioaccumulation, with the highest bioaccumulation factors (BAFd.w) in the brain and gonad, and detectable burdens in sperm. Neuroactive compounds showed increased brain and gonadal BAFd.w. over time. Effluent exposure altered key monoamine and amino acid NT levels and their precursors across tissues, accompanied by extensive reorganization of intra- and inter-tissue NT correlation networks. Cross-tissue analyses revealed persistent disruption of coordinated signaling along the brain-gonad-sperm axis.